Although other causative agents or conditions are now known, viruses are established as the etiologic agent in some types of malignancies in animals. One model accounting for acquisition of the virus induced malignant phenotype suggests a stable covalent attachment of viral DNA to animal cell DNA in a manner which resembles the interaction between bacteria and lysogenic bacteriophage: the covalent linking of oncogenic viral and animal genes involves recombination. Understanding virus-caused malignant transformation is the major objective of our long-range research objectives. We attempt in these studies to establish the function and location of viral genes involved in the induction of malignancy. "Model" studies involving wild type and mutant adenovirus 2 and adenovirus 12 in human and monkey cells (chronically or simultaneously coinfected with SV40) will be pursued to establish the in vivo parameters governing recombination. The immediate objectives of the studies include additional mapping of adenovirus 2 and adenovirus 12. Additional studies are planned which will establish how host genes function in virus-induced malignant transformation. Biochemical, genetic and physical experiments are proposed and defined which should aid in our understanding of the function of viral gene products in viral replication and viral oncogenesis.